Low Dose Ruxolitinib in Combination With Methylprednisolone

NCT04397367 | Completed Phase 1

• 1 other identifier: S-2019-177-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to determine the efficacy and safety of combined Low dose Ruxolitinib With Methylprednisone as Initial Therapy for the aGVHD(acute graft-versus-host disease )

Conditions

aGVHD; Stem Cell Transplant Complications

Outcome Measures

Primary Outcomes (1)

• complete remission rate of acute GVHD 28 days after enrollment.

  Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR) of acute GVHD

  Day 28 after treatment

Secondary Outcomes (5)

• the incidence of relapsed acute GVHD

  Day 90 after treatment

• Six-month duration of response

  Six-month after treatment

• Duration of response

  Day 90 after treatment

• Nonrelapse mortality (NRM)

  6 months after treatment

• Relapse rate

  2 years after treatment

Study Arms (4)

Ruxolitinib10 mg twice a day combined with Corticosteroids

EXPERIMENTAL

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 10 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Drug: Ruxolitinib 10 mg twice a day combined with Corticosteroids

Ruxolitinib5 mg twice a day combined with Corticosteroids

EXPERIMENTAL

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Drug: Ruxolitinib 5 mg twice a day combined with Corticosteroids

Ruxolitinib5 mg once a day combined with Corticosteroids

EXPERIMENTAL

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Drug: Ruxolitinib 5 mg once a day combined with Corticosteroids

Ruxolitinib 2.5 mg twice a day combined with Corticosteroids

EXPERIMENTAL

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 2.5 mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Drug: Ruxolitinib 2.5 mg once a day combined with Corticosteroids

Interventions

Ruxolitinib 10 mg twice a day combined with Corticosteroids DRUG

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 10 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Also known as: ruxolitinib 10 mg twice a day

Ruxolitinib10 mg twice a day combined with Corticosteroids

Ruxolitinib 5 mg twice a day combined with Corticosteroids DRUG

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Also known as: ruxolitinib 5 mg twice a day

Ruxolitinib5 mg twice a day combined with Corticosteroids

Ruxolitinib 5 mg once a day combined with Corticosteroids DRUG

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5 mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Also known as: Ruxolitinib 5 mg once a day

Ruxolitinib5 mg once a day combined with Corticosteroids

Ruxolitinib 2.5 mg once a day combined with Corticosteroids DRUG

Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 2.5 mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Also known as: Ruxolitinib 2.5 mg once a day

Ruxolitinib 2.5 mg twice a day combined with Corticosteroids

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosed with hematological diseases.
• Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies.
• new onset of grade II\~IV aGVHD or high risk aGVHD \[based on suppression of tumorigenicity 2 (also ST2), Regenerating Islet Derived Protein 3 Alpha (also REG3a), experimental objects) within 100 days post-transplantation.

You may not qualify if:

• recipients of second allogeneic stem cell transplant.
• acute GVHD induced by donor lymphocyte infusion, interferon.
• received first line aGVHD treatment before enrollment.
• overlap GVHD syndrome.
• pregnant or breast-feeding women.
• absolute neutrophil count (ANC) \<0.5×10e9/L or platelet count (PLT) \< 20×10e9/L
• Serum creatinine \> 2.0 mg/dL or creatinine clearance \< 40 mL/min measured or calculated by Cockroft-Gault equation.
• uncontrolled infection
• human immunodeficiency virus infection
• active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
• Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.
• allergic history to Janus kinase inhibitors.
• Severe organ dysfunction unrelated to underlying GVHD, including:
• Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction). Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy. Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
• Received Janus kinase inhibitor therapy after allo-HSCT for any indication.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Related Publications (7)

• Dou LP, Li HH, Wang L, Li F, Huang WR, Yu L, Liu DH. Efficacy and Safety of Unmanipulated Haploidentical Related Donor Allogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia. Chin Med J (Engl). 2018 Apr 5;131(7):790-798. doi: 10.4103/0366-6999.228243.

  PMID: 29578122 BACKGROUND

• Sandmaier BM, Kornblit B, Storer BE, Olesen G, Maris MB, Langston AA, Gutman JA, Petersen SL, Chauncey TR, Bethge WA, Pulsipher MA, Woolfrey AE, Mielcarek M, Martin PJ, Appelbaum FR, Flowers MED, Maloney DG, Storb R. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial. Lancet Haematol. 2019 Aug;6(8):e409-e418. doi: 10.1016/S2352-3026(19)30088-2. Epub 2019 Jun 24.

  PMID: 31248843 BACKGROUND

• Ruutu T, Gratwohl A, Niederwieser D, de Witte T, van der Werf S, van Biezen A, Mohty M, Kroger N, Rambaldi A, McGrath E, Sureda A, Basak G, Greinix H, Duarte RF. The EBMT-ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis. Bone Marrow Transplant. 2017 Mar;52(3):357-362. doi: 10.1038/bmt.2016.298. Epub 2016 Nov 28.

  PMID: 27892949 RESULT

• Akahoshi Y, Igarashi A, Fukuda T, Uchida N, Tanaka M, Ozawa Y, Kanda Y, Onizuka M, Ichinohe T, Tanaka J, Atsuta Y, Kako S; Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Impact of graft-versus-host disease and graft-versus-leukemia effect based on minimal residual disease in Philadelphia chromosome-positive acute lymphoblastic leukemia. Br J Haematol. 2020 Jul;190(1):84-92. doi: 10.1111/bjh.16540. Epub 2020 Mar 2.

  PMID: 32119132 RESULT

• Yeshurun M, Weisdorf D, Rowe JM, Tallman MS, Zhang MJ, Wang HL, Saber W, de Lima M, Sandmaier BM, Uy G, Kamble RT, Cairo MS, Cooper BW, Cahn JY, Ganguly S, Camitta B, Verdonck LF, Dandoy C, Diaz MA, Savani BN, George B, Liesveld J, McGuirk J, Byrne M, Grunwald MR, Drobyski WR, Pulsipher MA, Abdel-Azim H, Prestidge T, Wieduwilt MJ, Martino R, Norkin M, Beitinjaneh A, Seo S, Nishihori T, Wirk B, Frangoul H, Bashey A, Mori S, Marks DI, Bachanova V. The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Adv. 2019 Feb 26;3(4):670-680. doi: 10.1182/bloodadvances.2018027003.

  PMID: 30808685 RESULT

• Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.

  PMID: 26228813 RESULT

• Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Cell Therapy Transplant Canada. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020 Feb;7(2):e100-e111. doi: 10.1016/S2352-3026(19)30220-0. Epub 2020 Jan 17.

  PMID: 31958417 RESULT

MeSH Terms

Interventions

ruxolitinib; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Daihong Liu

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 17, 2020
• First Posted: May 21, 2020
• Study Start: January 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: December 31, 2020
• Last Updated: December 14, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)